Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis

“…In 2012, approximately 2.2 million new cancer cases were attributed to infections, among which helicobacter pylori ( H. pylori ), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV) play important roles ( Qu et al., 2021 ). Previous studies have confirmed that tumorigenesis is closely associated with a variety of pathogenic microorganisms comprising a heterogeneous assemblage of bacteria, fungi, protozoa, viruses, and phages ( Maiuri et al., 2017 ; Purcell et al., 2017 ; Tsoi et al., 2017 ; Kidane, 2018 ; Tsay et al., 2018 ; Zhang et al., 2018 ; Allen and Sears, 2019 ; Allen et al., 2019 ; Brennan and Garrett, 2019 ; Parhi et al., 2020 ; Valguarnera and Wardenburg, 2020 ; DeStefano Shields et al., 2021 ; Tsay et al., 2021 ) ( Table 2 ). Nejman et al.…”

“…Eight weeks following infection, inflammation-induced tumors in the distal colon have regions with increased levels of DNA methylation including the promoters of Hoxa5 and Polg relative to uninflamed epithelium and non-inflammation-induced tumors. Loss of the mismatch repair protein MSH2 abrogates inflammation-induced recruitment of DNMT1 and EZH2 to sites of acute oxidative DNA damage and DNA methylation alterations observed in inflammation-induced tumors [37]. These findings suggest that repair of oxidative base damage initially recruits epigenetic modifiers and sustained localization of these modifiers at sites of damage results in epigenetic alterations.…”

“…Recruitment of H3K4me3 to H3K27me3-labeled gene loci can prevent DNA methylation in Msh2 −/− mice [49]. Consistently, loss of Msh2 prevented promotor CpG island hypermethylation observed in inflammation-induced tumors [50].…”

“…In 2012, approximately 2.2 million new cancer cases were attributed to infections, among which helicobacter pylori ( H. pylori ), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV) play important roles ( Qu et al., 2021 ). Previous studies have confirmed that tumorigenesis is closely associated with a variety of pathogenic microorganisms comprising a heterogeneous assemblage of bacteria, fungi, protozoa, viruses, and phages ( Maiuri et al., 2017 ; Purcell et al., 2017 ; Tsoi et al., 2017 ; Kidane, 2018 ; Tsay et al., 2018 ; Zhang et al., 2018 ; Allen and Sears, 2019 ; Allen et al., 2019 ; Brennan and Garrett, 2019 ; Parhi et al., 2020 ; Valguarnera and Wardenburg, 2020 ; DeStefano Shields et al., 2021 ; Tsay et al., 2021 ) ( Table 2 ). Nejman et al.…”

“…Eight weeks following infection, inflammation-induced tumors in the distal colon have regions with increased levels of DNA methylation including the promoters of Hoxa5 and Polg relative to uninflamed epithelium and non-inflammation-induced tumors. Loss of the mismatch repair protein MSH2 abrogates inflammation-induced recruitment of DNMT1 and EZH2 to sites of acute oxidative DNA damage and DNA methylation alterations observed in inflammation-induced tumors [37]. These findings suggest that repair of oxidative base damage initially recruits epigenetic modifiers and sustained localization of these modifiers at sites of damage results in epigenetic alterations.…”

“…Recruitment of H3K4me3 to H3K27me3-labeled gene loci can prevent DNA methylation in Msh2 −/− mice [49]. Consistently, loss of Msh2 prevented promotor CpG island hypermethylation observed in inflammation-induced tumors [50].…”

“…In 2012, approximately 2.2 million new cancer cases were attributed to infections, among which helicobacter pylori ( H. pylori ), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV) play important roles ( Qu et al., 2021 ). Previous studies have confirmed that tumorigenesis is closely associated with a variety of pathogenic microorganisms comprising a heterogeneous assemblage of bacteria, fungi, protozoa, viruses, and phages ( Maiuri et al., 2017 ; Purcell et al., 2017 ; Tsoi et al., 2017 ; Kidane, 2018 ; Tsay et al., 2018 ; Zhang et al., 2018 ; Allen and Sears, 2019 ; Allen et al., 2019 ; Brennan and Garrett, 2019 ; Parhi et al., 2020 ; Valguarnera and Wardenburg, 2020 ; DeStefano Shields et al., 2021 ; Tsay et al., 2021 ) ( Table 2 ). Nejman et al.…”

“…Eight weeks following infection, inflammation-induced tumors in the distal colon have regions with increased levels of DNA methylation including the promoters of Hoxa5 and Polg relative to uninflamed epithelium and non-inflammation-induced tumors. Loss of the mismatch repair protein MSH2 abrogates inflammation-induced recruitment of DNMT1 and EZH2 to sites of acute oxidative DNA damage and DNA methylation alterations observed in inflammation-induced tumors [37]. These findings suggest that repair of oxidative base damage initially recruits epigenetic modifiers and sustained localization of these modifiers at sites of damage results in epigenetic alterations.…”

“…Recruitment of H3K4me3 to H3K27me3-labeled gene loci can prevent DNA methylation in Msh2 −/− mice [49]. Consistently, loss of Msh2 prevented promotor CpG island hypermethylation observed in inflammation-induced tumors [50].…”